Mitofusin 1 inhibits an apoptosis-associated amino-terminal conformational change in Bax, but not its mitochondrial translocation, in a GTPase-dependent manner

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Mitochondrial fusion and fission are dynamically regulated during apoptotic cell death, and mitofusin (Mfn) and related proteins have been shown to be involved in apoptosis-associated changes in mitochondrial morphology and function. Here, we investigated the involvement of Mfn proteins in the conformational activation and mitochondrial translocation of Bax, a key molecule responsible for apoptosis-associated mitochondrial changes. When ectopically expressed, Mfn1 inhibited the amino-terminal activation, but not the mitochondrial translocation, of Bax during staurosporine-induced apoptosis; overexpression of Mfn2 had no effect. Overexpression of Mfn1 mutants carrying point mutations in the GTPase domain (Mfn1-1038T and Mfn1-T109A) did not inhibit the amino-terminal activation of Bax. Furthermore, staurosporine-induced amino-terminal activation of Bax was significantly delayed in Mfn1-shRNA transfected (Mfn1-depleted) HeLa cells compared to cells transfected with control shRNA. These results collectively suggest a role for Mfn1 in regulating the activation of Bax on the outer mitochondrial membrane in a GTPase-dependent manner. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
Publisher
ELSEVIER IRELAND LTD
Issue Date
2012-10
Language
English
Article Type
Article
Keywords

CYTOCHROME-C RELEASE; INDUCED CELL-DEATH; ENDOPLASMIC-RETICULUM; MAMMALIAN-CELLS; FUSION; FISSION; PROTEIN; DYNAMICS; ACTIVATION; MORPHOLOGY

Citation

CANCER LETTERS, v.323, no.1, pp.62 - 68

ISSN
0304-3835
DOI
10.1016/j.canlet.2012.03.038
URI
http://hdl.handle.net/10203/102978
Appears in Collection
BS-Journal Papers(저널논문)BiS-Journal Papers(저널논문)
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